Drug interactions with solid tumour-targeted therapies

Abstract

Drug interactions are an on-going concern in the treatment of cancer, especially when targeted therapies, such as tyrosine kinase inhibitors (TKI) or mammalian target of rapamycin (mTOR) inhibitors, are being used. The emergence of elderly patients and/or patients with both cancer and other chronic co-morbidities leads to polypharmacy. Therefore, the risk of drug-drug interactions (DDI) becomes a clinically relevant issue, all the more so as TKIs and mTOR inhibitors are essentially metabolised by cytochrome P450 enzymes. These DDIs can result in variability in anticancer drug exposure, thus favouring the selection of resistant cellular clones or the occurrence of toxicity. This review provides a comprehensive overview of DDIs that involve targeted therapies approved by the FDA for the treatment of solid tumours for more than 3 years (sorafenib, sunitinib, erlotinib, gefitinib, imatinib, lapatinib, everolimus, temsirolimus) and medicinal herb or drugs. This review also provides some guidelines to help oncologists and pharmacists in their clinical practice.

Keywords: 5-fluorouracile; 5FU; ABC; ATP-binding cassette; AUC; BCRP; C(max); CYP; DDI; Drug–drug interactions; EIAEDS; Herb–drug interactions; Mammalian target of rapamycin inhibitors; P-glycoprotein; P-gp; Pharmacokinetics; Solid tumour; TKI; Targeted therapies; Tyrosine kinase inhibitors; UDP-glucuronyl transferase; UGT; area under the curve; breast cancer resistance protein; cytochrome p450 enzymes; drug–drug interactions; enzyme-inducing antiepileptic drugs; mTOR; mammalian target of rapamycin; maximum (peak) plasma concentration; tyrosine kinase inhibitor.